During the past decade it has been shown that the infection induced by H. pylori is the single most important factor in the development of gastritis. Gastritis induced by H. pylori is in fact one of the most common bacterial infections in the world. The infection causes an inflammation in the mucosa of the stomach, which, in some cases, slowly leads to the atrophy of the mucosa (atrophic gastritis).
A Helicobacter pylori infection is in itself symptomless. However, it predisposes the infected subject to ulcer diseases of the stomach and of the duodenum, and it also slightly increases the risk of stomach cancer. Once infected, the patient may carry the inflammation through his life, due to the lack of effective natural defense. After the infection, the same bacterial strain continues to grow inside the mucous layer on the surface of the mucous membrane.
The present treatment of H. pylori infection is based on the combination of one or more antibiotics together with bismuth preparations. Agents inhibiting gastric acid secretion (H.sub.2 -blockers and omeprazole) are also used for H. pylori eradication treatment. The treatment is difficult and, to be at all successful, it requires strong motivation and patience from both the patient and the doctor.
Combination therapy usually gives better H. pylori eradication than single drug therapy. Triple therapy (e.g. antibiotic/metronidazole/bismuth) for example, has been found to give better results than single drug therapy. One common combination used contains metronidazole (1200 mg/d), amoxicillin (1500 mg/d), and tetracycline (1550 mg/d), administered for two weeks and followed by bismuth subcitrate (480 mg/d) for four weeks. The other antibiotics used have usually been selected from the group consisting of ampicillin, penicillin, minocycline, doxycycline, erythromycin, clindamycin and ofloxacin, optionally in combination with metronidazole, tinidazole or furazolidone (Helicobacter pylori in Peptic Ulceration and Gastritis, ed. Marshall B. J. et al., Blackwell Scientific Publications, 1991, USA)
The problems associated with the present treatment relate to the development of resistant H. pylori strains, the reappearance of H. pylori after treatment, the long duration of the treatment and several side-effects (e.g. diarrhea caused by Clostridia difficile). This leads also to poor patient compliance.
On the other hand, it is previously known that exogenous phospholipids are of importance in the protection of the gastrointestinal tract (Lichtenberger et al., Science 219, 1327-1329, (1983)). It is assumed that the phospholipid molecules attach to the cell membranes with electrostatic bonds and direct their fatty acid side chains into the lumen, thus forming a uniform hydrophobic surface (Hills et al., Am. J. Physiol. 244, G561-G568 (1983)). Lichtenberger (EP publications 401 952 and 287 198) discloses methods employing compositions composed of mixtures of phospholipids and neutral lipids to treat the luminal lining of the gastrointestinal tract in the prevention or treatment of ulcerogenic processes. It is also generally well known to administer drugs, such as non-steroidal, anti-inflammatory drugs, together with phospholipids, and there is a number of publications relating thereto (e.g. DE 2856333). There is also a number of publications relating to the use of phospholipids of a specific composition for administration together with a variety of drugs for use in different manners of administration.
The phospholipid compositions have typically been formulated into colloidal or liposomal suspensions using an aqueous medium or diluent (EP publications 287 198). Especially liposome technology has advanced the delivery of drugs, diagnostic materials, cosmetics etc. Liposomes have been used to deliver drugs by encapsulating the drugs in the liposomes during their preparation, or alternatively, by combining the drugs with the liposomes following their formation (EP publication 249 561), and then administering them to the patient to be treated.
Liposomes are closed by one or several bilayer membranes containing an entrapped aqueous volume. The structure of the membrane bilayer is such that the hydrophobic `tails` of the lipid orient toward the centre of the bilayer while the hydrophilic `heads` orient towards the aqueous phase. The formation of a mixture of lipids into a bladder form can be accomplished by a number of ways, the original liposome preparation being disclosed by Bangham et al. (J. Mol. Biol. 13, 238-252, (1965)). The procedures used involve application of energy, such as by sonication or microfluidic procedures.
Liposomes prepared from synthetic phospholipids are of highest purity with required fatty acid composition and thus do not cause technical or analytical problems, as is the case with natural phospholipids. However, highly purified phospholipids of natural sources can be used.
However, there has so far been no effort to treat a Helicobacter pylori infection with a combination of phospholipid and a H. pylori eradicating antibiotic, prior to the present invention. The present inventors have now surprisingly discovered that a synergistic effect can be achieved in such a treatment.